title: PARP-1 modulates amyloid beta peptide-induced neuronal damage.
abstract: Amyloid beta peptide (Aβ) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ25-35 fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ25-35 induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Aβ25-35 exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Aβ25-35 induces DNA damage which in turn activates PARP-1. Challenge with Aβ25-35 is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Aβ25-35 via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Aβ and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed.
authors.affiliation: Department of Biochemical Sciences, Sapienza University, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Martire
authors.forename: Andrea
authors.initials: A
authors.lastname: Fuso
authors.forename: Dante
authors.initials: D
authors.lastname: Rotili
authors.forename: Italo
authors.initials: I
authors.lastname: Tempera
authors.forename: Cesare
authors.initials: C
authors.lastname: Giordano
authors.forename: Ivana
authors.initials: I
authors.lastname: De Zottis
authors.forename: Alessia
authors.initials: A
authors.lastname: Muzi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vernole
authors.forename: Grazia
authors.initials: G
authors.lastname: Graziani
authors.forename: Emanuela
authors.initials: E
authors.lastname: Lococo
authors.forename: Martina
authors.initials: M
authors.lastname: Faraldi
authors.forename: Bruno
authors.initials: B
authors.lastname: Maras
authors.forename: Sigfrido
authors.initials: S
authors.lastname: Scarpa
authors.forename: Luciana
authors.initials: L
authors.lastname: Mosca
authors.forename: Maria
authors.initials: M
authors.lastname: d'Erme
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D017931:DNA Primers; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases